Health problems in newborns of obese mothers

A growing number of studies imply that children born to obese mothers face health problems originating from the womb. Research from Tufts University suggests that low iron status is among these health problems, according to an analysis of maternal hepcidin, a hormone that is key in keeping iron levels balanced.

Transcript

Norman Swan: A growing issue that's concerning obstetricians and paediatricians is the effect of maternal obesity on pregnancy and the foetus. That's the interest of neonatal researcher Rimi Sen who's at Tufts University Medical Center in Boston.

Rimi Sen: We've been very interested in how maternal obesity affects micronutrient concentration. It stems from some animal work that I've done in the past looking at supplementation with various micronutrients and showing that the supplementation actually improved outcomes in offspring of obese rats.

Norman Swan: What sort of outcomes?

Rimi Sen: The primary outcome we looked at was body fat, and we found that adiposity was actually markedly decreased in rat pups born to mothers that were fed a diet that was supplemented with ACE and selenium.

Norman Swan: Vitamins A, C and E, and selenium, so essentially an antioxidant cocktail with a mineral supplement.

Rimi Sen: Exactly.

Norman Swan: Why on earth would a supplement with these vitamins affect the obesity of the pup?

Rimi Sen: What we speculated was that obesity in itself is a very pro-inflammatory state and a state that leads to high oxidative stress.

Norman Swan: And by pro-inflammatory you mean the immune system in the obese person is activated and irritable, if you like.

Rimi Sen: In a way it's the immune system that's activated, but in a way the immune system is also suppressed. So it's almost a double-edged sword in obesity where it is dis-regulated, the immune system. And so we speculated that the reason that this antioxidant cocktail improved offspring outcomes was because it actually down-regulated that inflammation and oxidative stress, and that the remodelling of the genes that occurred very early on in pregnancy was actually reversed by this antioxidant cocktail.

Norman Swan: So what you are postulating is that in fact the obesity changes the function of the genes in the foetus in some way with a so-called epigenetic effect. Rather than mutating the genes, it's how the genes work.

Rimi Sen: That's right.

Norman Swan: So you've done that in rats…

Rimi Sen: We've done that in rats.

Norman Swan: What evidence have you got in humans?

Rimi Sen: There are definite differences in micronutrient concentration in the blood. So certain vitamins that are protective against inflammation and oxidative stress are actually lower in obese pregnant women compared to lean pregnant women.

Norman Swan: Just before we move on to another micronutrient, iron, have you done any trials of supplementation in pregnant women and looking at their offspring?

Rimi Sen: Not yet.

Norman Swan: The history of antioxidant supplementation in humans has been profoundly disappointing.

Rimi Sen: Absolutely.

Norman Swan: It works on almost nothing.

Rimi Sen: That's right.

Norman Swan: So why should it work in this?

Rimi Sen: Right, and in pregnancy it has been tried in pre-eclampsia as well, which is a disease that is closely linked to oxidative stress. They also haven't seen an effect in that, but combining all the studies together what they found is that there is a possibility that in women who are obese, they might actually differentially benefit from this supplementation.

Norman Swan: Tell me about the studies on iron.

Rimi Sen: We were looking at a protein called hepcidin, a regulator of iron transport, and it's also expressed in the placenta. And so our interest was how hepcidin expression would affect this transmission, and what we found was that women who were obese, they did have a higher inflammation and this actually down-regulated the hepcidin expression and decreased the transport of iron from mother to foetus. So even though the obese and lean mothers had similar levels of iron in their blood, the foetuses…we measured iron levels in the cord blood, the foetuses actually had decreased iron in their cord blood.

Norman Swan: And is there any evidence that offspring of obese mothers are iron deficient to an extent that matters?

Rimi Sen: Neurodevelopment is critically affected by iron levels. There are some studies that have started to come out looking at neurodevelopment in the long term in infants born to obese mothers and have shown differences in neurodevelopmental indices.

Norman Swan: So if hepcidin is low in these women, presumably iron supplementation in the pregnant woman is not going to make a lot of difference if it's not going to be transported.

Rimi Sen: Right, and in the paper that we wrote we were very cautious about suggesting iron supplementation because we suspect that the basis of this is high inflammation which is leading to changes in hepcidin.

Norman Swan: So does that translate to an increased susceptibility to viral infections?

Rimi Sen: Yes, particularly influenza which we did see in the pandemic a few years ago, that obese pregnant women were one of the highest risk groups for not only contracting influenza but also for serious morbidity and mortality related to the disease. But there's also infections that obese pregnant women are susceptible to that can affect the health of their foetus.